tbuckley/cabot-search huggingface dataset:
Observational prospective study of physical activity in patients with cancer to define an objective performance status (OPS).
Authors: Eva Ruiz-Hispán, Tatiana Hernández, Bernard Doger de Spéville, Daniel Morillo, Ignacio Mahillo, Jesus Garcia-Foncillas, Victor Moreno
Journal: Journal of Clinical Oncology (2023)

1506 Background: Clinical trials in patients with advanced cancer rely on a good selection of candidates based on their functional status. The Eastern Cooperative Oncology Group (ECOG) Performance Status is the most frequently used in adult patients and is based on the subjective impression of the clinician during the interview with the patient. The current use of wearable devices will allow clinicians to assess the functional status of candidates for a clinical trial in a more objective way. We aim to define an “Objective Performance Status” (OPS) by measuring the daily physical activity of patients with metastatic cancer and correlating it with the classical prognostic variables. Methods: We prospectively measured daily physical activity with a wearable device in 111 patients with metastatic cancer during the screening period for a phase 1 clinical trial to avoid treatment interference with the functional status. Daily steps/distance and sleeping hours were measured and correlated with overall survival (OS) to define the OPS. Results: Full data was available for 70 patients. Median survival was gradually shorter as physical activity decreases (HR 5.76 (95% CI 2.98-11.1) P &lt; 0001). The cut off selected to define the OPS was determined by univariate survival analysis and showed that patients who walk less than 1200 meters per day have 5 times the risk of mortality (poor OPS). Median OS was 3.2 months (95% CI 2.5-5.8) P &lt; 0001) for patients with poor OPS and 11.2 months for patients with good OPS (95% CI 7.2-31.3 P &lt; 0001). Conclusions: The objective assessment of performance status (OPS) using a wearable device to monitor the physical activity in patients with cancer is an independent prognostic factor for survival and is an objective predictor of mortality.[Table: see text]
Incidence and outcomes of cardiac tamponade in patients with breast cancer.
Authors: Nosakhare Paul Ilerhunmwuwa, Mustafa Wasifuddin, Narek Hakobyan, Muhammad Tahir, Boris Avezbakiyev
Journal: Journal of Clinical Oncology (2023)

e13108 Background: Cardiac tamponade (CT) is a cardio-oncological emergency reported to be associated with poor outcomes in some solid tumors, such as lung cancers. There is a paucity of literary evidence on CT in patients with breast cancer. We sought to examine the Nationwide Inpatient Sample (NIS) -the largest inpatient database in the United States- to determine the incidence and factors associated with CT, and the in-hospital outcomes in patients with breast cancer. Methods: We retrospectively explored the NIS database collected from 2016 to 2020. Patients aged ≥ 18 with breast cancer and CT were selected using ICD-10 diagnostic codes. Univariate, multivariate logistic, and negative binomial regression models were used to assess the annual incidence trends, determine factors associated with cardiac tamponade and in-hospital outcomes among patients with breast cancer. Results: A total of 144,405 breast cancer patients (weighted n= 722,025) were examined, of which 345 (0.24%) had CT. The incidence of CT rose from 25 per 10 000 in 2016 to 27.3 per 10 000 cases of breast cancer in 2020 though this was not statistically significant (p=0.409). Patients with CT were more likely to be younger (60 ± 13 vs 66 ± 14, p&lt;0.001), with comorbidity index ≥ 5 (90.72% vs 9.28%, p&lt;0.0001), history of chemotherapy (18.84% vs 12.46%, p=0.0004), history of radiation therapy (17.97% vs 10.80%, p&lt;0.0001), and had Medicare (50.43% vs 49.57%, p&lt;0.001). After multivariate adjustment, comorbidity index ≥ 5 (aOR=5.16, 95% CI: 3.03 - 8.78; p&lt;0.001), and history of irradiation (aOR=1.45, 95% CI: 1.08 - 1.96; p=0.014), were found to be independent predictors of CT. However, the risk of CT was less with age &gt; 65 years (aOR=0.64, 95% CI: 0.47 - 0.87; p=0.004). Regarding in-hospital outcomes, after controlling for other covariates, CT was associated with an increased risk of mortality (aOR=1.71, 95% CI: 1.16 - 2.52; p=0.07) and longer hospital stay (7.25 ± 5.77 vs 4.78 ± 5.45; incidence risk ratio [IRR]:1.49, 95% CI: 1.36 - 1.63; p &lt;0.001). Conclusions: Cardiac tamponade is rare in breast cancer and tends to occur more in patients who are younger, have comorbidities, and prior radiation therapy. It is associated with increased risk of in-hospital mortality and longer stay. Risk stratification of patients with breast cancer when deciding treatment is relevant to reduce the likelihood of CT and improve outcomes. Further studies are needed to establish the optimal management of CT in patients with breast cancer.
Knowledge and use of different breast cancer screening tools among primary care physicians: A cross-sectional study.
Authors: Natalia Camejo, Dahiana Amarillo, Moira Bernate, Florencia Burguez, Eliana Darino, Adrian Deleon, Tatiana Milwa, Maria Barcia, Gabriel David Krygier
Journal: Journal of Clinical Oncology (2023)

e13673 Background: In Uruguay, breast cancer (BC) is the leading cause of cancer incidence and mortality in women. Objective: To understand the implementation of BC screening among primary care physicians in routine clinical practice and the degree of adherence to the recommendations put forward in 2015 by the Ministry of Public Health (MPH) for the early detection of BC. Methods: This was a descriptive, cross-sectional, observational study. An anonymous survey was administered to physicians working in primary care. Results: 169 physicians were included, 89.4% (151) consider the use of screening mammography decreases mortality from BC, 54.4% (92) indicate mammography from 40 years of age and 38.5% (65) from 50 years of age. The majority (56.8%, 96) indicate mammography every 2 years in the population of women aged 50-69 years. Of the respondents, 65.7% (111) were aware of the national guidelines and 47.9% (81) followed them, while 18.9% (32) followed recommendations from other scientific bodies. Conclusions: This study showed that primary care physicians make correct use of the different BC screening tools. Active measures are needed to develop educational programs for healthcare personnel, which may enable them to disseminate knowledge and positively influence patients' attitudes.
Real-world comparison of triplet- versus doublet-chemotherapy with bevacizumab in patients with newly diagnosed metastatic colorectal cancer (mCRC).
Authors: William Joseph Chapin, Wei-Ting Hwang, Ronac Mamtani, Mark H. O'Hara
Journal: Journal of Clinical Oncology (2023)

3574 Background: Meta-analysis of five randomized intensification trials in mCRC demonstrated an overall survival (OS) benefit of triplet chemotherapy (5FU/leucovorin, oxaliplatin, irinotecan) plus bevacizumab (Triplet/Bev) compared to doublet chemotherapy plus bevacizumab (Doublet/Bev) (HR 0.81). Guidelines recommend first-line Triplet/Bev for patients with excellent performance status and normal organ function who can withstand increased toxicity, but such patients are less represented in the real world. In this retrospective cohort study, we examine the real-world effectiveness of Triplet/Bev compared to Doublet/Bev in the U.S. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data curated via technology-enabled abstraction from ~ 280 cancer clinics. Included were mCRC patients treated with first-line Triplet/Bev or Doublet/Bev between 10/23/14 and 10/31/22. OS by treatment was assessed using the Kaplan Meier method and adjustment for confounding variables was performed using Cox proportional hazards modeling with stabilized inverse probability of treatment weighting (IPTW). Pre-specified confounding variables included age, gender, race/ethnicity, year of metastatic diagnosis, health insurance, practice setting, KRAS/NRAS/BRAF mutation status, MMR/MSI status, synchronous/metachronous metastases, primary tumor sidedness, CEA, renal dysfunction, hepatic dysfunction, and ECOG performance status. Missing data were imputed using multiple imputation with chained equations. Results: Among 10,016 patients, 391 (3.9%) received Triplet/Bev and 9,625 (96.1%) received Doublet/Bev. Patients who received Triplet/Bev were younger (median age 52 vs 63 years) and were more likely to be treated at academic practices (27% vs 8%), to have synchronous metastatic disease (83% vs 65%), and to have KRAS/NRAS/BRAF wild-type disease (30% vs 17%). In the univariate analysis, median OS was 30.0 months (95% CI 24.7 – 34.7) in the Triplet/Bev cohort versus 23.4 months (95% CI 22.8 – 24.1) in the Doublet/Bev cohort (HR 0.73; 95% CI 0.62 – 0.85; p &lt; 0.001). In Cox proportional hazards modeling with IPTW, there was no significant difference in hazard of death between Triplet/Bev and Doublet/Bev (HR 0.92; 95% CI 0.75 – 1.12; p = 0.4). Conclusions: In this large, national, real-world population of patients with mCRC, first-line treatment with Triplet/Bev was not associated with improved survival compared to Doublet/Bev after accounting for differences in baseline patient characteristics. The benefit to Triplet/Bev observed in randomized trials does not translate well to a more heterogeneous, real-world population. Sub-group analyses including by age, tumor sidedness, KRAS/NRAS/BRAF status, and baseline CEA level will be performed.
Depth of radiographic response (DpR) and time to tumor regrowth (TTG) to predict overall survival following anti-VEGF therapy in recurrent glioblastoma.
Authors: Benjamin M. Ellingson, Akifumi Hagiwara, Connor Morris, Nicholas Cho, Sonoko Oshima, Francesco Sanvito, Talia Oughourlian, Catalina Raymond, Lauren E. Abrey, Josep Garcia, Dana T. Aftab, Colin Hessel, Tamar Rachmilewitz Minei, Shifra Fain Shmueli, David Nathanson, Patrick Y. Wen, Timothy Francis Cloughesy
Journal: Journal of Clinical Oncology (2023)

2063 Background: Anti-angiogenic therapies, anti-VEGF agents, cause high radiographic response rates due to reduction in vascular permeability. However, we theorized the degree of tumor shrinkage combined with the duration of response might be a more meaningful measure of tumor control and may better reflect real patient benefit. In the current study, we investigate the association between model-derived parameters describing enhancing tumor volumetric dynamics and overall survival (OS) in recurrent glioblastoma treated with anti-VEGF therapy from multiple clinical trials. Methods: N=134 patients treated with bevacizumab +/- irinotecan (BRAIN Trial; NCT00345163) and N=121 patients treated with cabozantinib (XL184-201; NCT00704288) were used to identify potential imaging biomarkers, and N=63 patients in the bevacizumab control arm in a phase III trial (GLOBE Trial; NCT02511405) were used as a validation dataset. Enhancing tumor volumes were estimated using T1 subtraction maps, and a biexponential model was used to model tumor response ( d) and regrowth ( g) rates, as well as time to tumor regrowth ( TTG), the inflection point where the tumor stops shrinking and starts to regrow, and the depth of response ( DpR) after initiation of anti-VEGF therapy for each patient. Log-rank, univariate, and multivariable Cox regression were used to quantify the relationship of these parameters and OS. Results: Optimized thresholds based on maximum hazard ratio occurred at d =0.11 months -1 ( P=5x10 -9 training; P=0.0082 validation); g=0.07 months -1 ( P=5x10 -20 training; P&lt;0.0001 validation); TTG of 3.8 months ( P=6x10 -17 training; P&lt;0.0001 validation); and DpR of 11.3% ( P=0.0026 training; P=0.0177 validation). Univariate and multivariable Cox regression using these thresholds and controlling for age and baseline tumor volume confirmed that d, g, TTG, and DpR were all significant and independent predictors of OS in both phase II training and phase III validation datasets ( P&lt;0.01). Additionally, patients exhibiting combinations of a high DpR and/or long TTG showed differential median OS, while patients with favorable diffusion MR phenotypes exhibited a longer OS and significantly longer TTG. Conclusions: Volumetric response and regrowth rates, TTG, and DpR using a biexponential model are significant and independent predictors of OS in recurrent glioblastoma treated with anti-VEGF therapy. Clinical trial information: NCT00345163 ; NCT00704288 ; NCT02511405 .
“You matter”: Patient reported outcomes on cancer disparities related to the COVID-19 pandemic.
Authors: Mohamed Mohanna, Saad Sabbagh, Barbara Dominguez, Mira Itani, Ludovic Saba, Sindu Iska, Hong Liang, Caroline Diaz, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2023)

e13674 Background: Disparities in cancer care have been exacerbated by the COVID-19 pandemic. Understanding the challenges encountered by patients can help alleviate the burden of cancer and improve access to care. Methods: We recruited consecutive patients with cancer at a comprehensive academic cancer center and analyzed patient reported socioeconomic and mental health challenges, and their perception of access to care since the start of the pandemic using a modified version of the You Matter: COVID-19 Mental Health Impact Survey. The survey instrument was self-administered once from November 11, 2022 to January 12, 2023 and consisted of 21 items with questions focused on demographics, social health, telehealth attitudes, and mental health. Established patients diagnosed at the cancer center prior to the start of the COVID-19 pandemic and who are continuing care were included in the study. Results: A total of 136 participants were included in this analysis. Participants characteristics were as follows: 70% had age&gt;65, 75% white, 70% female, 43 % had bachelor's degree or higher, 62.5% with non-private insurance, 95% maintained same insurance throughout the pandemic, and 80% had household of &gt; 1 person. Since April 2020, 49.3% reported increased level of stress and 60.6% reported increased anxiety, stress or experience of distress as a direct result of COVID-19. Among the patients that reported they had participated in telehealth, 84.4% described it as easy and effective, and 70.6% found it either comfortable or neutral. Black participants were more likely to have less contact with providers compared to white participants (OR=5.54, p=0.0180); participants age ≥65 were more likely to report worse overall health compared to younger participants (OR=2.67, p=0.0359); male participants were more likely to experience challenges because of COVID-19 (OR=2.12, p=0.0496), were less uncomfortable with telehealth (OR=0.034, p=0.0350), had increased anxiety and stress, and experienced less distress due to COVID19 (OR=0.47, p=0.0490) compared to female participants. Conclusions: Challenges reported during the COVID-19 pandemic varied across sociodemographic groups, with elderly, male and black reporting the worst impact related to the pandemic. The vast majority of the survey participants reported increased stress, anxiety, or distress affecting quality of life and hindering access to care. The results of the study, however, suggest the important role of telehealth in addressing challenges and narrowing disparities in access to cancer care across the majority of participants.
Influence of CD47 on CD8<sup>+ </sup>T-cell and tumor prognosis based on pan-cancer analysis.
Authors: Hongxin Liang, Lintong Yao, Daipeng Xie, Hongrui Qiu, Zenan Lin, Hao Li, Jinhang Leng, Huili Wang, Xiuwei Jiao, Liyun Qiu, HaiYu Zhou
Journal: Journal of Clinical Oncology (2023)

e14699 Background: CD47 was an immune checkpoint, constituting the CD47/SIRPα axis, sending the 'Do not eat me' signal to macrophages, hereby promoting immune escape of tumor cells in the tumor immune microenvironment(TIME). The role of CD47 has been proved affected immunotherapy efficacy and patient outcomes. However, how it affects TIME, specifically on CD8 + T-cell in pan-cancer, has not been fully illustrated. Therefore, we aimed to identify it, which could help us to gain insights into potential anti-cancer treatment. Methods: We used a lot of R package and computational tools to analysis of differential gene expression, prognosis, immunoinfiltration, pathway enrichment and Correlation. Single-cell sequencing and multiple immunofluorescence staining were uesd to verify our hypothesis. Data was based on 17,382 samples given by 948 healthy individuals from GTEx, 39 cancer types from TCGA, 79 databases and 2045746 cells from tumor patients and healthy donors in TISCH, and our real-world sample. Datasets were normalized for estimation of the TME components at both the single-cell and annotated cluster levels. Our study investigated the role of CD47 in prognosis and TIME, mainly from the view of adaptive immunity. Results: CD47 was expressed in nearly all cancer types, associated with worse prognosis in various cohorts in pan-cancer(p＜0.05) compared to the normal tissues. Then, we found CD47 was better correlated with tumor immune evasion through T-cell infiltration compared with T-cell rejection in multi-cancers. And we detected high CD47 expression with high CD8 + T-cell infiltration had a worse prognosis. So we hypothesis high CD47 could linked with T-cell exhausted. Then, we investigated that genetic alterations and oncogenic characteristics of CD47 were concomitant with the CD8 + T-cell exhausted by analysis of pathway and gene in mulit-cancer especially squamous-cell carcinomas. Finally, we proved CD47 synergy with CD8 + T-cell exhausted genes in LUSC and ESCA by single-cell analysis and multiple immune fluorescence staining. Conclusions: CD47 is highly associated with CD8 + T-cell exhausted and may induce cancer immune evasion leading to a worse prognosis. Thus, CD47 and T-cell exhausted correlated genes may serve as dual antigenic targets and provide insights into potential immunotherapy.
Cost and time estimates for integrating a cardiovascular health application for cancer survivors in the electronic health record: Case studies from the NCORP network.
Authors: Randi E. Foraker, Michael Durkin, Ian Lackey, Kevin Heard, Brian J. Wells, Susan Fesperman, Eleanor Davidson, Philip Payne, Albert M. Lai, Melissa Gendron, Kathryn E. Weaver
Journal: Journal of Clinical Oncology (2023)

e13557 Background: Clinical decision support (CDS) tools may support the delivery of guideline concordant cancer care yet must be integrated into EHR platforms and optimized for clinical workflow. Implementation outcomes are not well-documented in the literature for deployment of CDS tools in community oncology practices. Here we provide best practices for teams looking to implement CDS tools in diverse cancer care settings. Methods: The Automated Heart-Health Assessment (AH-HA-WF-1804CD) study is a clinic-randomized trial coordinated by the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base to support cardiovascular health assessment among cancer survivors. The AH-HA team developed and guided the implementation of the AH-HA tool, an EHR-based CDS visualization of the American Heart Association's Life's Simple 7 modifiable risk factors supplemented with cancer treatment information. Four NCORP clinics were randomized to the intervention arm and implemented the tool within their EHR leveraging Fast Healthcare Interoperable Resources (FHIR) standards and best practice advisories (BPAs). Information technology (IT) team authorization was required prior to randomization. We provided an implementation checklist to each clinic alongside virtual support from experts in implementing CDS for research and operational purposes. We describe our successful CDS tool implementation strategy and report the timeline for implementation at each clinic. Results: Although all clinics utilized the same EHR platform (Epic), clinics differed in terms of their time to approval, implementation, and tool activation, ranging in a total from 4 to 15 months. Although we provided step-by-step guidance for CDS deployment, each site required at least one technical assistance consultation. The estimated cost at each implementation site to deploy the tool, given a range of 40 to 80 hours at $150/hour, was $6,000 to $12,000 US dollars. Conclusions: Strengths of the implementation process included extensive documentation and clear communication of the steps for implementation. Clinics desired flexibility to adapt BPAs to their workflows. Site-level differences may pose challenges for interpretation of study implementation outcomes, including patient-level reach measures. Studies testing the impact of similar CDS tools should plan for clinic-level adaption and consider variability in timelines and assistance needed within the overall study timeline and budget. Clinical trial information: NCT03935282 .
Clinical and molecular characterization of a cohort with breast cancer brain metastases.
Authors: Emmanuella Oyogoa, Brie Chun, Lyndsey Sandow, Douglas Rice, Shaun Goodyear, Alexandra Dos Santos Zimmer
Journal: Journal of Clinical Oncology (2023)

e13122 Background: Breast cancer (BC) is the most common cancer in Women in the United States, it is the second most frequent cause of brain metastases (BM). Despite steady improvement in BC treatment (tx) and prognosis, BM continues to be an unmet need. With most BM patients excluded from clinical trials, the study of cohorts remains an important source of information regarding this aspect of the disease. We aim to characterize incidence, disease course, tx, and molecular profile of BM for BC subtypes. Methods: In this single-center retrospective analysis, we identified all adult patients (&gt;18 years) diagnosed (dx) with BC as well as secondary malignant neoplasm of the brain from 1/1/15 to 10/1/22 using database query from EMR. Baseline characteristics were obtained through chart review. Molecular profiling was performed in a total of 41 patients, 8 of which was from brain tissue. Next generation sequencing (NGS) was the most used method. Results were generated using descriptive statistics. Results: We identified 304 BC patients with BM (median age = 60 years [range: 24 to 88]). Baseline characteristics are described in table 1. Hormone receptor positive/HER2-neu negative (HR+/HER2-) was the most commonly observed BC subtype (41.4%), and triple negative BC (TNBC) was the least frequent (16.8%). On primary tissue biopsy, five patients with recurrent BC had a subtype shift that differed from their initial disease: 2 patients with HR +/HER2 – BC subtype recurred with TNBC, 2 patients with a HR+/HER2- recurred with HR+/HER2+ BC, and 1 patient with TNBC at initial dx had their disease shift to HR+/HER 2- BC at first metastatic recurrence then back to TNBC 4 years after initial dx. NGS was available for 41 patients, with TP53, MSS, PIK3CA and ERBB2 being the most frequently observed mutations. On average, 3 lines of therapy were used before dx of BM. In the metastatic setting, capecitabine was one the most commonly used drugs. Targeted central nervous system (CNS) tx used in this study population include WBRT, SRS, SBRT and surgical resection. Conclusions: Studying patterns of disease presentation, progression during standard tx, and the molecular characteristics accompanying BM will enable us to develop more effective tx for patients. Our cohort includes a spectrum of BC subtypes and natural histories. Further characterization of this cohort with tx interactions, progression and survival timeline is ongoing and will be reported at the meeting. [Table: see text]